Antioxidantien und Selen gehören nicht in einen Topf – Bewertung der Supplementierung während Chemo- oder Strahlentherapie bei Brustkrebs

Lomustin und Temozolomid in Kombination mit Bestrahlung

A dedicated cloud system for real-time upfront quality assurance in pediatric radiation therapy Abstract Purpose Pediatric radiotherapy (RT) is a highly specialized field, requiring great experience to delineate correctly tumor targets and organs at risk. To reduce treatment failures related to planning inaccuracies and to obtain robust clinical results despite the limited numbers of enrolled pediatric patients, the SIOP PNET5MB clinical trial on medulloblastoma requires a real-time, pre-radiation review of the RT treatment (craniospinal irradiation and boost plan) under the direct responsibility of the national coordinator center. Here we describe the centralized radiotherapy quality assurance (QA) program developed in Italy for this purpose. Methods Using the software package VODCA (MSS, Hagendorn, Switzerland, www.vodca.ch), we developed a cloud platform able to handle computed tomography (CT) images and RT objects and to support the complete workflow required by the review process in the context of the SIOP PNET5 trial. Results All Italian centers participating in the PNET5 trial adopted the proposed QA system. 24 patients were successfully enrolled and reviewed. For 15 patients (62.5%), one or more plan revisions were requested for the craniospinal irradiation plan and for 11 patients (45.8%) plan revisions were requested for the boost. RT was delivered after the plan was centrally approved for all enrolled patients. So far, in Italy, no patients have been excluded from PNET5 due to dosimetric incompliance to the protocol or for exceeding the RT starting time limit. Conclusion The cloud platform successfully supported the trial workflow, producing official review documents. This efficient QA was crucial to guarantee optimized treatments and protocol compliance for all pediatric patients enrolled in the SIOP protocol.

Radiomic analysis of planning computed tomograms for predicting radiation-induced lung injury and outcome in lung cancer patients treated with robotic stereotactic body radiation therapy Abstract Objectives To predict radiation-induced lung injury and outcome in non-small cell lung cancer (NSCLC) patients treated with robotic stereotactic body radiation therapy (SBRT) from radiomic features of the primary tumor. Methods In all, 110 patients with primary stage I/IIa NSCLC were analyzed for local control (LC), disease-free survival (DFS), overall survival (OS) and development of local lung injury up to fibrosis (LF). First-order (histogram), second-order (GLCM, Gray Level Co-occurrence Matrix) and shape-related radiomic features were determined from the unprocessed or filtered planning CT images of the gross tumor volume (GTV), subjected to LASSO (Least Absolute Shrinkage and Selection Operator) regularization and used to construct continuous and dichotomous risk scores for each endpoint. Results Continuous scores comprising 1–5 histogram or GLCM features had a significant (p = 0.0001–0.032) impact on all endpoints that was preserved in a multifactorial Cox regression analysis comprising additional clinical and dosimetric factors. At 36 months, LC did not differ between the dichotomous risk groups (93% vs. 85%, HR 0.892, 95%CI 0.222–3.590), while DFS (45% vs. 17%, p < 0.05, HR 0.457, 95%CI 0.240–0.868) and OS (80% vs. 37%, p < 0.001, HR 0.190, 95%CI 0.065–0.556) were significantly lower in the high-risk groups. Also, the frequency of LF differed significantly between the two risk groups (63% vs. 20% at 24 months, p < 0.001, HR 0.158, 95%CI 0.054–0.458). Conclusion Radiomic analysis of the gross tumor volume may help to predict DFS and OS and the development of local lung fibrosis in early stage NSCLC patients treated with stereotactic radiotherapy.

Prognostic factors in patients with T1 glottic cancer treated with radiotherapy Abstract Purpose Presentation of long-term results of radiation treatment in patients with T1 glottic cancer and evaluation of prognostic factors. Methods We performed a retrospective analysis in a group of 569 patients with T1 squamous cell glottic carcinoma treated with radiotherapy at the Center of Oncology in Cracow between 1977 and 2007. In all, 503 (88%) patients presented with T1a stage disease and 66 (12%) with T1b. Anterior commissure infiltration was present in 179 (31%) patients. Average hemoglobin level prior to therapy was 13.9 g/dl. Using the body mass index (BMI), 114 (20%) patients were underweight, and 91 (16%) were overweight. Median time between collecting tumor specimen and beginning of radiotherapy was 56 days (range 14–145 days). Treatment regimen was normofractionated with single fraction ≤2 Gy in 102 (18%) and hypofractionated in 467 (82%) patients. Results The 5‑ and 10-year overall survival (OS), disease-specific survival (DSS) and local control (LC) rates were 85 and 68%, 88 and 86%, 89 and 87%, respectively. Multivariate analysis showed that tobacco smoking, low hemoglobin level (<13 g/dl), anterior commissure infiltration, fraction dose ≤2 Gy and time from collecting specimen to beginning of therapy longer than 30 days had negative impact on LC and DSS. Patients’ age over 60 years, worse performance status and malnutrition (BMI <18.5) had negative impacts on OS. Conclusions Radiotherapy is a highly effective treatment method in patients with T1N0M0 glottic cancer. LC and DSS may be improved following hypofractionation, smoking cessation, and shortening of waiting-time until start of treatment. OS was mainly influenced by nutritional and performance status.

Definitive radiotherapy vs. postoperative radiotherapy for lower gingival carcinomas of the mandible Abstract Purpose To assess radiotherapy (RT) outcomes in patients with gingival carcinoma and growth up to or involvement of the lower jaw bone. Methods This was a retrospective analysis of 51 patients with squamous cell carcinomas of the gingiva. Patients received definitive (group 1, 31.4%) or postoperative (group 2, 66.7%) RT between 2005 and 2017 at the Department of Radiation Oncology, University Hospital Heidelberg. The primary endpoint was overall survival (OS) in both treatment groups. Other endpoints were local-disease-free survival (LDFS), progression-free survival (PFS) and treatment-related toxicity (Common Terminology Criteria for Adverse Events, CTCAE, Version 4.03). Results Median age at first diagnosis was 63 years. All patients had a local advanced disease (American Joint Commission on Cancer [AJCC] stage III–IV). After a median follow-up of 22 months (range 3–145 months), 20 patients (39.2%) were still alive. At 5 years, OS rate was 36.6%. No significant differences in OS (p = 0.773), PFS (p = 0.350) and LDFS (p = 0.399) were observed between the two groups. Most common higher-grade acute RT-related complications (≥ grade 3) were dermatitis (78.2%), oral mucositis (61.7%), xerostomia (51.5%), and loss of taste (74.6%). Three cases (5.8%) of osteoradionecrosis (ORN) of the lower jaw were detected after 15–31 months. Conclusions Definitive and postoperative RT have similar treatment outcomes for patients with lower gingiva carcinomas of the lower jaw. The most common acute complications (grade ≥3) were dermatitis, oral mucositis, xerostomia and loss of taste.

Radiogenomics in head and neck cancer: correlation of radiomic heterogeneity and somatic mutations in TP53, FAT1 and KMT2D Abstract Purpose Genetic tumour profiles and radiomic features can be used to complement clinical information in head and neck squamous cell carcinoma (HNSCC) patients. Radiogenomics imply the potential to investigate complementarity or interrelations of radiomic and genomic features, and prognostic factors might be determined. The aim of our study was to explore radiogenomics in HNSCC. Methods For 20 HNSCC patients treated with primary radiochemotherapy, next-generation sequencing (NGS) of tumour and corresponding normal tissue was performed. In total, 327 genes were investigated by panel sequencing. Radiomic features were extracted from computed tomography data. A hypothesis-driven approach was used for radiogenomic correlations of selected image-based heterogeneity features and well-known driver gene mutations in HNSCC. Results The most frequently mutated driver genes in our cohort were TP53 (involved in cell cycle control), FAT1 (Wnt signalling, cell–cell contacts, migration) and KMT2D (chromatin modification). Radiomic features of heterogeneity did not correlate significantly with somatic mutations in TP53 or KMT2D. However, somatic mutations in FAT1 and smaller primary tumour volumes were associated with reduced radiomic intra-tumour heterogeneity. Conclusion The landscape of somatic variants in our cohort is well in line with previous reports. An association of somatic mutations in FAT1 with reduced radiomic tumour heterogeneity could potentially elucidate the previously described favourable outcomes of these patients. Larger studies are needed to validate this exploratory data in the future.

PET/MRI-guided GTV delineation during radiotherapy planning in patients with squamous cell carcinoma of the tongue Abstract Purpose The aim of the study was to evaluate the usefulness and accuracy of 18-fluorine-labeled fluorodeoxyglucose (PET) and magnetic resonance imaging (MRI) hybrid in gross tumor volume (GTV) delineation during radiotherapy planning in patients with carcinoma of the tongue. Methods Ten patients with squamous cell carcinoma (SCC) of the tongue underwent computed tomography (CT) and PET/MRI examination. The GTV for primary tumor and lymph nodes (nGTV) were defined on CT (GTV-CT) and compared to GTVs obtained from PET (GTV-PET) and MRI (GTV-MRI) images. Two methods of GTV determination were used: visual interpretation of CT, PET (GTV-PETvis) and MRI images and quantitative automatic method (Syngovia, Siemens) based on a chosen threshold value (20%, 30%, 40%, 50%) of standardized uptake values (SUVmax) from PET examination (GTV-PET20%, GTV-PET30%, etc.). Statistical analysis of differences in GTV values obtained from CT, PET and MRI studies was performed. GTV-CT was used as a reference. Results In all, 80% of GTV-MRI and 40% of GTV-PETvis were larger than GTV-CT. Respectively, 20% of GTV-MRI and 60% of GTV-PETvis were smaller than GTV-CT. Taking into account all threshold measurements, 70% of volumes were smaller than GTV-CT. GTV-PET30% were the most closely related volumes to GTV-CT from all threshold methods in 50% of patients. GTV-PETvis generated the most similar volumes in relation to GTV-CT from all PET measurements. Statistical analysis confirmed those results. Compared to nGTV-CT, 70% of nGTV-MRI and 20% of nGTV-PETvis were larger. The remaining nGTV-MRI and nGTV-PETvis measurements were smaller than nGTV-CT. Measurements of all thresholds nGTVs were smaller than nGTV-CTV in 52.5% of cases. nGTV-PET20% were the most closely related volumes to nGTV-CT in 40% of the cases. Statistical analysis showed that nGTV-PET20% (p = 0.0468), nGTV-PETvis (p = 0.0166), and nGTV-PET50% (p = 0.0166) diverge significantly from nGTV-CT results. nGTV-MRI (p = 0.1141), nGTV-PET30% (p = 0.2845), and nGTV-PET40% (p = 0.5076) were significantly related with nGTV-CT. Conclusion Combination of PET/MRI provides more information during target tumor mass delineation in radiotherapy planning of patients with SCC of the tongue than other standard imaging methods. The most frequently matching threshold value was 30% of SUVmax for primary tumor delineation and 30–40% of SUVmax for nGTV determination.

Pembrolizumab ist effektiver und besser verträglich als Methotrexat, Docetaxel oder Cetuximab bei rezidivierten oder metastasierten HNO-Karzinomen (KEYNOTE-040)

Predicting survival and local control after radiochemotherapy in locally advanced head and neck cancer by means of computed tomography based radiomics Abstract Purpose To appraise the ability of a radiomics signature to predict clinical outcome after definitive radiochemotherapy (RCT) of stage III–IV head and neck cancer. Methods A cohort of 110 patients was included in a retrospective analysis. Radiomics texture features were extracted from the gross tumor volumes contoured on planning computed tomography (CT) images. The cohort of patients was randomly divided into a training (70 patients) and a validation (40 patients) cohorts. Textural features were correlated to survival and control data to build predictive models. All the significant predictors of the univariate analysis were included in a multivariate model. The quality of the models was appraised by means of the concordance index (CI). Results A signature with 3 features was identified as predictive of overall survival (OS) with CI = 0.88 and 0.90 for the training and validation cohorts, respectively. A signature with 2 features was identified for progression-free survival (PFS; CI = 0.72 and 0.80); 2 features also characterized the signature for local control (LC; CI = 0.72 and 0.82). In all cases, the stratification in high- and low-risk groups for the training and validation cohorts led to significant differences in the actuarial curves. In the validation cohort the mean OS times (in months) were 78.9 ± 2.1 vs 67.4 ± 6.0 in the low- and high-risk groups, respectively, the PFS was 73.1 ± 3.7 and 50.7 ± 7.2, while the LC was 78.7 ± 2.1 and 63.9 ± 6.5. Conclusion CT-based radiomic signatures that correlate with survival and control after RCT were identified and allow low- and high-risk groups of patients to be identified.